Organ Engineering Research Articles

Programmable degrading engine powered photoactivated organic colloidal motors

Owing to environmental and health concerns, engineered nanobots are confronting tremendous challenges in the practical transition to industrial and civil applications. Even if the nanomaterials are made of biodegradable components, they still need to suffer a long-time decomposing process to completely destroy the nanostructures. Here, we report a straightforward and scalable preparation of light-driven organic colloidal motors assembled by macromolecular payloads and photoactivated azo-containing polymer engines through a continuous nanoprecipitation process. In response to UV irradiation, the light-fueled polymer engine enables converting light to chemical energy by photodegrading the polymer-aggregated phase into short-chained biodegradable residues and environmental-friendly nitrogen gas. The release behavior of the nitrogen independent of the surrounding chemical medium can be conveniently programmed for on-demand powering the motors (up to ∼120 μm/s) to carry out transport missions in various complicated environments (e.g. high viscous and high ionic solution, tumor matrix). The organic polymer engine can be completely deconstructed after the mission accomplishment for relieving potential environmental risks of the engineered nanomachines.

Lymphatic Tissue and Organ Engineering for In Vitro Modeling and In Vivo Regeneration.

The lymphatic system has an important role in maintaining fluid homeostasis and transporting immune cells and biomolecules, such as dietary fat, metabolic products, and antigens in different organs and tissues. Therefore, impaired lymphatic vessel function and/or lymphatic vessel deficiency can lead to numerous human diseases. The discovery of lymphatic endothelial markers and prolymphangiogenic growth factors, along with a growing number of in vitro and in vivo models and technologies has expedited research in lymphatic tissue and organ engineering, advancing therapeutic strategies. In this article, we describe lymphatic tissue and organ engineering in two- and three-dimensional culture systems and recently developed microfluidics and organ-on-a-chip systems in vitro. Next, we discuss advances in lymphatic tissue and organ engineering in vivo, focusing on biomaterial and scaffold engineering and their applications for lymphatic vessels and lymphoid organ regeneration. Last, we provide expert perspective and prospects in the field of lymphatic tissue engineering.

Designing a Network of Crystalline Polymers for a Scalable, Nonfluorinated, Healable and Amphiphobic Solid Slippery Interface.

The fluorinated-liquid infused amphiphobic slippery interfaces exhibiting superior sliding of the beaded oil/water droplets, often suffer from durability and contamination issues. Here, the ability of 1) hexagonal packing of hydrocarbon sides in a selected "comb-like" polymer and 2) its reversible phase transition at 51 °C was rationally exploited to achieve temperature-assisted rapid (<1 minute) and repetitive (50 times) self-healable amphiphobic solid-slippery coating on both planar and geometrically-complex substrates. The selected "comb-like" polymer was strategically infused in a porous, hydrophilic and thick (≈4.8 μm) polymeric coating. The resultant solid and smooth interface exhibited sliding of beaded droplets of various liquids, including droplets of water, polar (ethanol, 1-propanol, 1-hexanol, DMSO, DMF), and non-polar (decane, dodecane, diiodomethane) organic solvents, edible (vegetable oil), motor, engine (petrol, diesel, kerosene) and crude oils.

Designing a Network of Crystalline Polymers for a Scalable, Nonfluorinated, Healable and Amphiphobic Solid Slippery Interface

AbstractThe fluorinated‐liquid infused amphiphobic slippery interfaces exhibiting superior sliding of the beaded oil/water droplets, often suffer from durability and contamination issues. Here, the ability of 1) hexagonal packing of hydrocarbon sides in a selected “comb‐like” polymer and 2) its reversible phase transition at 51 °C was rationally exploited to achieve temperature‐assisted rapid (&lt;1 minute) and repetitive (50 times) self‐healable amphiphobic solid‐slippery coating on both planar and geometrically‐complex substrates. The selected “comb‐like” polymer was strategically infused in a porous, hydrophilic and thick (≈4.8 μm) polymeric coating. The resultant solid and smooth interface exhibited sliding of beaded droplets of various liquids, including droplets of water, polar (ethanol, 1‐propanol, 1‐hexanol, DMSO, DMF), and non‐polar (decane, dodecane, diiodomethane) organic solvents, edible (vegetable oil), motor, engine (petrol, diesel, kerosene) and crude oils.

Role of Biomolecules and Biologics in Precision Medicine, Personalized Medicine, and Emerging Therapies

In the 1990s, DNA sequencing technologies could only read bite-sized pieces of DNA. Then came the human genome project (HGP), a thirteen-year international effort, 1990-2003, with the primary goal of discovering the complete set of human genes, sequencing nucleotides, and making the information accessible worldwide for further biological studies. We have come a long way since that time in terms of sequencing the genes of the human genome. Now the researchers can sequence the DNA and analyze gene-expressed proteins in individual cells, allowing them to dissect the complexities of genetic diseases with exceptional details. Currently, technologies are available for single-cell or multi-omics platforms to analyze genotype and phenotype. The completion of this one-of-a-kind project created public expectations for immediate, better health care delivery and possible cures for 'so called' incurable diseases. The HGP was the single most influential investment made in modern basic science research. A monumental breakthrough in medicine has given us the ability to sequence the DNA in cancer cells to identify possible errors in mutations. The impact of the HGP's success was so significant that President Barack Obama initiated a very ambitious new 'precision medicine' research initiative and announced the launch of this project during his State of the Union Address in 2015. The benefits of precision and personalized medicine include predicting susceptibility to diseases, improving disease diagnostics, preempting disease progression, customizing disease prevention strategies, and developing personalized drugs and therapies. As examples of emerging therapies, we have discussed the role of biomolecules and biologics in precision medicine applications like 'The All of Us,' personalized medicine approaches for monogenic diseases like hemophilia, sickle cell disease, and other rare genetic disorders, and CRISPR gene-editing technologies. Biomolecules play an essential role in all life processes, a variety of signaling processes, which are vital for normal functioning of physiological responses, in the early diagnosis of risk factors for various diseases, in the development of diseases and their progress. Furthermore, biomolecules, RNAs, DNAs, molecular and cellular engineering, genetic engineering of biologics, cells, tissues, and organs, play an important role in emerging therapeutic applications. The majority of the therapies discussed in this review are regulated as biologics under the Public Health Services Act of the USA. There is great interest in developing targeted therapy or precision medicine therapy for monogenic diseases, organ transplant applications, and tumor management, designed to interfere with targeted molecules for cancer-causing genes to slow the spread of cancer cells. Because molecular engineering, the development of biologics, gene-editing applications, and biomanufacturing are key components of emerging therapies, a keynote series was organized at INTERPHEX in November of 2021. INTEPHEX is the premier event that offers the latest intelligence, cutting-edge technologies, and state-of-the-art innovation for product development for pharmaceutical and biotechnology platforms. In an earlier article in this journal, we described drug discovery and development in the COVID Age; this overview provides a birds-eye view of the salient findings in each emerging area of medicine—precision medicine, personalized medicine, and emerging therapies.

A multi-axis robot-based bioprinting system supporting natural cell function preservation and cardiac tissue fabrication.

Despite the recent advances in artificial tissue and organ engineering, how to generate large size viable and functional complex organs still remains as a grand challenge for regenerative medicine. Three-dimensional bioprinting has demonstrated its advantages as one of the major methods in fabricating simple tissues, yet it still faces difficulties to generate vasculatures and preserve cell functions in complex organ production. Here, we overcome the limitations of conventional bioprinting systems by converting a six degree-of-freedom robotic arm into a bioprinter, therefore enables cell printing on 3D complex-shaped vascular scaffolds from all directions. We also developed an oil bath-based cell printing method to better preserve cell natural functions after printing. Together with a self-designed bioreactor and a repeated print-and-culture strategy, our bioprinting system is capable to generate vascularized, contractible, and long-term survived cardiac tissues. Such bioprinting strategy mimics the in vivo organ development process and presents a promising solution for in vitro fabrication of complex organs.

Biomedical materials to repair damaged tissues and organs in sports dance performances

Micro-nano manufacturing of inorganic—organic composite tissue and organ engineering scaffolds is a field of biomaterial research that has emerged in recent years. Cell scaffolds for repairing damaged tissues and organs composed of degradable materials are one of its core technologies. Based on this research background, the article analyzes the efficacy of bone scaffold biomedical materials implanted in the injured leg caused by dance exercise. And through finite element analysis and elastic modulus analysis of the bracket’s stress and strain curves. The study found that the stiffness of the bone scaffold biomedical material is reduced after entering the human body. Biomedical materials can exert their toughness characteristics under the action of human bone proteins.

POS-827 THE EFFECTS OF PERFUSATE DENSITY AND DURATION ON THE VASCULAR STRUCTURE AND FUNCTION OF DECELLULARIZED AND RECELLULARIZED WHOLE KIDNEY SCAFFOLDS IN VITRO

Chronic kidney disease is a progressive condition in which the optimal functionally restorative therapy is organ transplantation. Due to increasing demand, regenerative medicine approaches have been proposed as possible therapeutic alternatives, such as whole organ engineering. This research focuses on the changes that occur in the decellularized and recellularized kidney’s architecture and vasculature after perfusion with low and high-density fluids at several flow rates.

Translation of 3D printed materials for medical applications.

During the past 30 years, 3D printing (3DP) technologies significantly influenced the manufacturing world, including innovation in biomedical devices. This special issue reviews recent advances in translating 3DP biomaterials and medical devices for metallic, ceramic, and polymeric devices, as well as bioprinting for organ and tissue engineering, along with regulatory issues in 3DP biomaterials. In our introductory article, besides introducing selected 3DP processes for biomaterials, current challenges and growth opportunities are also discussed. Finally, it highlights a few success stories for the 3D printed biomaterials for medical devices. We hope these articles will educate engineers, scientists, and clinicians about recent developments in translational 3DP technologies.

Tuning the photoreactivity of photocycloaddition by halochromism

Harnessing the power of light for chemical transformation is a long-standing goal in organic synthesis, materials fabrication and engineering. Amongst all photochemical reactions, [2 + 2] photocycloadditions are inarguably the most important and most frequently used. These photoreactions have green characteristics by enabling new bond formation in a single step procedure under light irradiation, without the need for heat or chemical catalysis. More recently, substantial progress has been made in red-shifting the activation wavelength of photocycloadditions in response to research trends moving towards green and sustainable processes, and advanced applications in biological environments. In the past 5 years, our team has further expanded the toolbox of photocycloaddition reactions that can be triggered by visible light. In our exploration of photochemical reactivity, we found that reactivity is often red-shifted compared to the substrate’s absorption spectrum. Our efforts have resulted in red-shifted photochemical reactions, providing some of the lowest energy – and catalyst-free – photo-activated [2 + 2] cycloadditions (up to 550 nm). More recently, we introduced an additional level of control over such finely wavelength gated reactions by altering the pH of the reaction environment, thus exploiting halochromic effects to enhance or impede the photoreactivity of red-shifted [2 + 2] photocycloaddition reactions. In this account, we discuss the current state of halochromically regulated photochemical reactions and their potential in soft matter materials on selected examples.

Enhanced performance and stability of low-bandgap mixed lead–tin halide perovskite photovoltaic solar cells and photodetectors via defect passivation with UiO-66-NH2 metal–organic frameworks and interfacial engineering

The incorporation of the UiO-66-NH2 metal–organic frameworks as the processing additive into mixed lead–tin halide perovskites can effectively passivate the defects, enabling the photovoltaic devices to exhibit high performance and good stability.

Achieving Air/Water Stable and Photocatalytically Active Ge-Containing 2D Halide Perovskites by Organic Spacer Engineering

Achieving Air/Water Stable and Photocatalytically Active Ge-Containing 2D Halide Perovskites by Organic Spacer Engineering

Rapid Chromium Reduction by Metal-Free Organic Polymer Photocatalysis Via Molecular Engineering

Rapid Chromium Reduction by Metal-Free Organic Polymer Photocatalysis Via Molecular Engineering

Organic spacer engineering in 2D/3D hybrid perovskites for efficient and stable solar cells

The PMAI-based PSCs form multiple NH⋯I hydrogen bonds, which can passivate interface defects and suppress ion migration and diffusion.

Switchable Supramolecular Jalousie Constructed from a Fluorenone Macrocycle

Organic crystal engineering is a promising strategy to construct functional materials. Herein, we demonstrate that the marriage of organic crystal engineering and macrocyclic chemistry yields a supramolecular jalousie that can be reversibly opened and closed in crystals. The synchronous rotation of fluorenone units in macrocycles triggered by toluene/phenylmethanol vapor contributes to such motions. This supramolecular jalousie is assembled from a trimeric fluorenone macrocycle, which is synthesized in 46% yield by the condensation of a 2,7-bis(2,4-dimethoxyphenyl)fluorenone monomer with paraformaldehyde. Mechanistic studies indicate that the large size (∼1.6 nm) and the rigid skeleton of the trimeric fluorenone macrocycle provide enough space for the rotation of fluorenone units as well as the encapsulation of guests in the solid state. Moreover, the bistable conformations and induced-fit structural adjustment guarantee such switchable single-crystal-to-single-crystal transformations.

DNA-mediated molecular assembly of a triphenylene–surfactant complex monolayer

Bottom-up DNA-guided molecular assembly is a technique of choice in modern organic device engineering. DNA, being a polyelectrolyte, is capable of mediating electrostatic interactions between different molecular building blocks. Here, we report DNA-mediated molecular assembly of an electrostatically driven triphenylene-surfactant complex monolayer. The monolayer, formed at air-water interface with DNA in the subphase, was studied using surface manometry and Brewster angle microscopy. Unlike that of the pristine system, the monolayer in presence of DNA showed enhanced stability and a remarkably high efficiency of deposition on solid supports. The morphologies of deposited films with controlled number of layers were studied using atomic force microscopy. In addition, UV–visible spectroscopy and grazing incidence X-ray diffraction (GIXRD) technique confirmed the presence of DNA in the deposited films. Since both triphenylene and surfactant are technologically relevant molecules, the DNA-mediated molecular assemblies deposited on solid substrates could find applications as functional materials in organic electronics.

A Pulmonary Vascular Model From Endothelialized Whole Organ Scaffolds.

The development of an in vitro system for the study of lung vascular disease is critical to understanding human pathologies. Conventional culture systems fail to fully recapitulate native microenvironmental conditions and are typically limited in their ability to represent human pathophysiology for the study of disease and drug mechanisms. Whole organ decellularization provides a means to developing a construct that recapitulates structural, mechanical, and biological features of a complete vascular structure. Here, we developed a culture protocol to improve endothelial cell coverage in whole lung scaffolds and used single-cell RNA-sequencing analysis to explore the impact of decellularized whole lung scaffolds on endothelial phenotypes and functions in a biomimetic bioreactor system. Intriguingly, we found that the phenotype and functional signals of primary pulmonary microvascular revert back—at least partially—toward native lung endothelium. Additionally, human induced pluripotent stem cell-derived endothelium cultured in decellularized lung systems start to gain various native human endothelial phenotypes. Vascular barrier function was partially restored, while small capillaries remained patent in endothelial cell-repopulated lungs. To evaluate the ability of the engineered endothelium to modulate permeability in response to exogenous stimuli, lipopolysaccharide (LPS) was introduced into repopulated lungs to simulate acute lung injury. After LPS treatment, proinflammatory signals were significantly increased and the vascular barrier was impaired. Taken together, these results demonstrate a novel platform that recapitulates some pulmonary microvascular functions and phenotypes at a whole organ level. This development may help pave the way for using the whole organ engineering approach to model vascular diseases.

Creating Organic Functional Materials beyond Chemical Bond Synthesis by Organic Cocrystal Engineering.

Organic cocrystal engineering refers to two or more organic molecules stoichiometrically combined and held together by noncovalent intermolecular interactions, which differs from standard chemical synthesis involving covalent bond breakage and formation. Organic cocrystals have unique properties and offer a new strategy for creating enhanced organics. First, however, some key questions need to be addressed: How do diverse monomers affect the intermolecular interaction kinetics during cocrystallization? How do the intermolecular forces in cocrystals affect cocrystal functions? In this Perspective, the definition and advantages of organic cocrystal engineering, specifically in the construction of a reliable intermolecular interaction-stacking structure-performance relationship, are outlined. Additionally, recent developments in the field and the questions above are discussed. Finally, a brief conclusion and some hints on likely future developments are provided.

Decellularized Whole-Organ Pre-vascularization: A Novel Approach for Organogenesis.

Introduction: Whole-organ decellularization is an attractive approach for three-dimensional (3D) organ engineering. However, progress with this approach is hindered by intra-vascular blood coagulation that occurs after in vivo implantation of the re-cellularized scaffold, resulting in a short-term graft survival. In this study, we explored an alternative approach for 3D organ engineering through an axial pre-vascularization approach and examined its suitability for pancreatic islet transplantation. Methods: Whole livers from male Lewis rats were decellularized through sequential arterial perfusion of detergents. The decellularized liver scaffold was implanted into Lewis rats, and an arteriovenous bundle was passed through the scaffold. At the time of implantation, fresh bone marrow preparation (BM; n = 3), adipose-derived stem cells (ADSCs; n = 4), or HBSS (n = 4) was injected into the scaffold through the portal vein. After 5 weeks, around 2,600 islet equivalents (IEQs) were injected through the portal vein of the scaffold. The recipient rats were rendered diabetic by the injection of 65 mg/kg STZ intravenously 1 week before islet transplantation and were followed up after transplantation by measuring the blood glucose and body weight for 30 days. Intravenous glucose tolerance test was performed in the cured animals, and samples were collected for immunohistochemical (IHC) analyses. Micro-computed tomography (CT) images were obtained from one rat in each group for representation. Results: Two rats in the BM group and one in the ADSC group showed normalization of blood glucose levels, while one rat from each group showed partial correction of blood glucose levels. In contrast, no rats were cured in the HBSS group. Micro-CT showed evidence of sprouting from the arteriovenous bundle inside the scaffold. IHC analyses showed insulin-positive cells in all three groups. The number of von-Willebrand factor-positive cells in the islet region was higher in the BM and ADSC groups than in the HBSS group. The number of 5-bromo-2′-deoxyuridine-positive cells was significantly lower in the BM group than in the other two groups. Conclusions: Despite the limited numbers, the study showed the promising potential of the pre-vascularized whole-organ scaffold as a novel approach for islet transplantation. Both BM- and ADSCs-seeded scaffolds were superior to the acellular scaffold.

3D printing of self-standing and vascular supportive multimaterial hydrogel structures for organ engineering.

Three dimensional printable formulation of self-standing and vascular-supportive structures using multi-materials suitable for organ engineering is of great importance and highly challengeable, but, it could advance the 3D printing scenario from printable shape to functional unit of human body. In this study, the authors report a 3D printable formulation of such self-standing and vascular-supportive structures using an in-house formulated multi-material combination of albumen/alginate/gelatin-based hydrogel. The rheological properties and relaxation behavior of hydrogels were analyzed before the printing process. The suitability of the hydrogel in 3D printing of various customizable and self-standing structures, including a human ear model, was examined by extrusion-based 3D printing. The structural, mechanical, and physicochemical properties of the printed scaffolds were studied systematically. Results supported the 3D printability of the formulated hydrogel with self-standing structures, which are customizable to a specific need. In vitro cell experiment showed that the formulated hydrogel has excellent biocompatibility and vascular supportive behavior with the extent of endothelial sprout formation when tested with human umbilical vein endothelial cells. In conclusion, the present study demonstrated the suitability of the extrusion-based 3D printing technique for manufacturing complex shapes and structures using multi-materials with high fidelity, which have great potential in organ engineering.